Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
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DOI：
10.1016/j.immuni.2021.09.002
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发表时间：
2021-11-09
期刊：
影响因子：
32.4
通讯作者：
Nattermann J
中科院分区：
文献类型：
--
作者：
Krämer B;Knoll R;Bonaguro L;ToVinh M;Raabe J;Astaburuaga-García R;Schulte-Schrepping J;Kaiser KM;Rieke GJ;Bischoff J;Monin MB;Hoffmeister C;Schlabe S;De Domenico E;Reusch N;Händler K;Reynolds G;Blüthgen N;Hack G;Finnemann C;Nischalke HD;Strassburg CP;Stephenson E;Su Y;Gardner L;Yuan D;Chen D;Goldman J;Rosenstiel P;Schmidt SV;Latz E;Hrusovsky K;Ball AJ;Johnson JM;Koenig PA;Schmidt FI;Haniffa M;Heath JR;Kümmerer BM;Keitel V;Jensen B;Stubbemann P;Kurth F;Sander LE;Sawitzki B;Deutsche COVID-19 OMICS Initiative (DeCOI);Aschenbrenner AC;Schultze JL;Nattermann J
对先天免疫系统的纵向分析，包括最早的时间点，对于了解冠状病毒病（COVID-19）的免疫发病机制和临床过程至关重要。在这里，我们使用单细胞转录组学和蛋白质组学以及功能研究对来自四个独立队列的205例患者（403个样本;症状发作后第2至41天）的自然杀伤（NK）细胞进行了详细的表征。我们发现早期重度COVD-19患者的干扰素（IFN）-α血浆水平升高，同时IFN刺激基因（ISG）和参与IFN-α信号传导的基因的NK细胞表达增加，而在中度疾病中观察到肿瘤坏死因子（TNF）诱导基因的上调。NK细胞发挥抗SARS-CoV-2（严重急性呼吸综合征冠状病毒2）活性，但在严重COVID-19中功能受损。此外，NK细胞功能障碍可能与严重COVID-19中纤维化肺病的发展相关，因为NK细胞表现出抗纤维化活性受损。我们的研究表明，在重度和中度COVID-19中，IFN-α和TNF应答分别优先，并将IFN-α诱导的NK细胞应答延长与疾病结局较差相关联。NK细胞在对病毒感染的先天性反应中的重要性为更深入地了解其在COVID-19中的作用提供了理论基础。在这里，克雷默等人。利用NK细胞的纵向分析，分别显示与中度和重度COVID-19相关的早期TNF和IFN-α特征，以及严重疾病中的NK细胞功能损伤。
Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome. The importance of NK cells in the innate response to viral infection provides rationale for deeper understanding of their role in COVID-19. Here, Krämer et al. utilize longitudinal analysis of NK cells to show early TNF and IFN-α signatures associated with moderate and severe COVID-19, respectively, and NK cell functional impairment in severe disease.
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危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
影响因子：
4.3
作者：
Chen H;Lau MC;Wong MT;Newell EW;Poidinger M;Chen J
通讯作者：
Chen J
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
8
作者：
Alvarez, Maite;Simonetta, Federico;Negrin, Robert S.
通讯作者：
Negrin, Robert S.
影响因子：
48
作者：
Browaeys, Robin;Saelens, Wouter;Saeys, Yvan
通讯作者：
Saeys, Yvan